Between 1985 and 1991, approximately 30,000 persons in Linxian, China participated in two nutritional intervention trials that tested the effect of various mineral and vitamin supplements on esophageal and gastric cancer. In 1991, when the intervention phase of the studies ended, we found beneficial effects of vitamin E, selenium, and beta-carotene on cancer mortality and incidence, and beneficial effects of a multivitamin supplement on the progression of pre-malignant disease and on stroke mortality. This year we completed a follow-up study that consisted of interview, physical examination and selected endoscopic examinations. In the coming year these data will be analyzed to see how the effects we found have evolved in the post-treatment period. We also initiated seven cancer etiology studies that use serum collected in 1985 from the study participants. We designed these studies to determine how serologic evidence of nutritional status, fungal contamination of foods, and certain viral and bacterial infections predict subsequent mortality and morbidity in these people, and to see whether the treatment effects we found differ in serologically defined subsets. We have just completed the second year of our intervention trial in Shandong, China. This is a multi-factorial study that tests whether treatment for H. pylori, supplementation with vitamin E, vitamin C, and selenium, and supplementation with a garlic extract, lowers the prevalence of gastric dysplasia. Of the 3411 participants randomized at the start of the study, only 10 have been lost to follow-up. Compliance with the assigned pills has been excellent, with greater than 90% of participants taking all their assigned pills as assessed by pill disappearance. Serum measures of pill compliance show a significant increase of vitamin levels and garlic metabolites in the groups receiving the active treatments when compared to those receiving placebo. From preliminary data on H. pylori eradication, it appears that the success of our treatment protocol in eliminating H. pylori was greater than 70%. To date, there have been no serious unfavorable reactions to any of the intervention agents. The effect on pubertal development of the therapy for acute lymphoblastic leukemia (ALL) was studied in 188 female survivors of ALL. Though the risk of disordered menarche was low, subjects less than 8 years old receiving 1800 cGy cranial radiation, and subjects receiving 2400 cGy below the diaphragm, had earlier and later menarche respectively than did their female siblings.